Background: Several case reports of the onset or exacerbation of multiple sclerosis or other demyelinating conditions shortly after vaccination have suggested that vaccines may increase the risk of demyelinating diseases.

Objective: To evaluate the association between vaccination and onset of multiple sclerosis or optic neuritis.

Design: Case-control study involving cases of multiple sclerosis or optic neuritis among adults 18 to 49 years of age. Data on vaccinations and other risk factors were obtained from computerized and paper medical records and from telephone interviews.

Setting: Three health maintenance organizations.

Participants: Four hundred forty case subjects and 950 control subjects matched on health maintenance organization, sex, and date of birth.

Interventions: None.

Main outcome measures: Onset of first symptoms of demyelinating disease at any time after vaccination and during specified intervals after vaccination (<1 year, 1-5 years, and >5 years).

Results: Cases and controls had similar vaccination histories. The odds ratios (95% confidence intervals), adjusted for potential confounding variables, of the associations between ever having been vaccinated and risk of demyelinating disease (multiple sclerosis and optic neuritis combined) were 0.9 (0.6-1.5) for hepatitis B vaccine; 0.6 (0.4-0.8) for tetanus vaccination; 0.8 (0.6-1.2) for influenza vaccine; 0.8 (0.5-1.5) for measles, mumps, rubella vaccine; 0.9 (0.5-1.4) for measles vaccine; and 0.7 (0.4-1.0) for rubella vaccine. The results were similar when multiple sclerosis and optic neuritis were analyzed separately. There was no increased risk according to timing of vaccination.

Conclusion: Vaccination against hepatitis B, influenza, tetanus, measles, or rubella is not associated with an increased risk of multiple sclerosis or optic neuritis.